Enhanced plaque vulnerability is associated with elevated levels of vascular endothelial growth factor (VEGf) and its receptors (VEGFR} expressed on endothelial, smooth muscle cells, and monocyteslmacrophages in plaques. VEGFNEGFR signaling increases plaque vulnerability through three interrelated processes; enhanced angiogenesjs, recruitment of monocyteslmacrophages, and vascular permeability resulting in local hemorrhage. Since the prevalence of VEGFNEGFR is increased in highly vulnerable plaques, VEGFR imaging may provide valuable information oo plaque vulnerability. We developed a family of tracers for multi-modal VEGFR imaging based oo human dimeric VEGF converted into a single-chain scVEGF. We have recently established that scVEGF-based SPECT tracers can be used for reliable imaging of VEGFRs in atherosclerotic plaques, distinguishing higher VEGFR prevalence in vulnerable plaques in diabetic ApoE-1- mice vs plaques of low vulnerability in non-diabetic ApoE-1- mice. We propose to 1) optimize these tracers to maximize specific plaque uptake, improve clearance and biodistribution characteristics, and 2) test feasibility of constructing tracers that image separately VEGFR-1 and VEGFR-2 that could provide more detailed information oo the processes responsible for development of plaque vulnerability.